Lecture 4

Question 1

What processes can be enriching for antibodies that recognise the CD4 Binding site of HIV gp120?

Answer 1

create a probe that mimicks the CD4 binding site

create a variant that has a single amino acid change within the CD4 binding sit

Select for antibodies that bind the probe (b12), but not the variant - ie retain CD4 binding site recognition

Question 2

What is the large scale isolation of bNt mabs (vaccines) from memory B cells

Answer 2

1. Sort single IgG B cells that bind a modified gp160 trimer called 2CC
2. recover the igV genes from each cell
3. Re-express as a recombinant, comlete IgG in a test tube

Question 3

What are the six hallmark capabilities of a cancer cell?

Answer 3

Sustained proliferative signalling

Evading growth suppressors

Acivating invasion and metastasis

Enabling replicative immortality

Inducing angiogenesis

Resisting cell dealth

Question 4

Moleucles that promote BCell cancer must:

promote __ ____

extend cell ___ ____by enhancing survival

enable DNA _____

Answer 4

promote cell proliferation

extend cell life span by enhancing survival

enable DNA mutation

Question 5

There are special properties of B cells which pre dispose them to malignancies, what are they?

Answer 5

They deliberately damage their DNA

AID-generated somatic hypermutations affecting the variable (V) regions of genes encoding immunoglobulins

AID is currently considered the master regulator of secondary antibody diversification because it is involved in the initiation of three distinct immunoglobulin diversification processes: somatic hypermutation (SHM), class-switch recombination (CSR), and gene-conversion (GC).

Question 6

most cancers come out of ___

Answer 6

GCs

Question 7

Burkitt Lymphoma involves the translocation of Myc into the ____ ____ locus

Answer 7

Burkitt Lymphoma involves the transfer of Myc in the Heavy chain locus

Question 8

Follicular lymphoma involves translocation of ______ genes into the immunoglobulin locus

Answer 8

Follicular lymphoma involves translocation of apoptosis genes into the immunoglobulin locus

Question 9

Myc anc cyclins are cell cycle and growth regulators

they…

Answer 9

promote cell divison

Question 10

bcl2 and ____
are cell survival proteins

they…

Answer 10

bcl2 and bclX

extend life span

Question 11

____ and ___

are

DNA damage sensors

(increase genomic instability/utation)

Answer 11

bcl6 and p53

Question 12

Myc: transcription factor

Drives _____

regulates cell _____

Inhibits ________

Myc is a very strong proto-_______

Answer 12

Myc: transcription factor

Drives proliferation

regulates cell growth

Inhibits differentiation

Myc is a very strong proto-oncogene

Question 13

Under stress, cells activate ___-only, overwhelm ___ and trigger _____by perforating mitochondria, releasing cyt C and ultimately, activation of ________

Answer 13

Under stress, cells activate BH3-only, overwhelm bcl2 and trigger apoptosis by perforating mitochondria, releasing cyt C and ultimately, activation of caspases

Question 14

What does overexpression of bcl2 lead to

Answer 14

blockng apopto

sis

Question 15

____ inhibits the DNA damage response in GC B cells

Answer 15

bcl 6

expression is absolutely required for GC to form

Question 16

Translocaitona nd mutation can cause bcl6 to act unnaturaly, so ___ damage occurs _________
(while also inhibitiing differentiation)

Answer 16

Translocaitona nd mutation can cause bcl6 to actualy unnaturaly, so DNA damage occurs UNCHECKED

(while also inhibitiing differentiation)

Question 17

In usmmary, what are the mutations tha convert bcl6 into an oncogene?

Answer 17

transloactions that lead to continued expression

somatic mutations that stop transcription from being repressed

also mutations that stop bcl6 from being dgrated - increased stability